The JMJD4 Knockout SK-HEP-1 Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal knockout cell population with targeted disruption of the JMJD4 gene in the SK-HEP-1 human hepatocellular carcinoma cell line. This loss-of-function model is designed for researchers investigating the roles of JMJD4 in translational regulation, epigenetic modification, and oxygen sensing within liver cancer contexts. The polyclonal population ensures genetic diversity while maintaining functional relevance for pooled experiments and bulk assays.
SK-HEP-1 is an epithelial cell line originally isolated from the ascitic fluid of a male patient with liver adenocarcinoma. It is widely employed as a model system for hepatic tumorigenesis, metastatic progression, and chemotherapeutic drug sensitivity. The SK-HEP-1 background recapitulates key aspects of aggressive liver cancer phenotypes, including anchorage-independent growth and migratory potential, making it a suitable host for studying genes implicated in hepatocellular carcinoma pathophysiology.
JMJD4 encodes a histone and protein lysine demethylase belonging to the iron and 2-oxoglutarate-dependent dioxygenase family. It catalyzes the demethylation of eukaryotic elongation factor 1A1 (eEF1A1) at lysine 36, thereby modulating translation elongation fidelity and rates. JMJD4 activity is regulated by oxygen levels, availability of cofactors iron (Fe2+) and 2-oxoglutarate, and potentially by HIF-1?? transcriptional control. Downstream, its demethylation of eEF1A1 directly influences ribosome function via the 60S ribosomal subunit, while its oxygenase activity may also affect HIF-1?? stability through interactions with prolyl hydroxylases and the von Hippel-Lindau protein, linking cellular hypoxia sensing to global translation. JMJD4 participates in pathways involving eEF1A1, histone H3/H4 lysine residues, and the HIF-1?? hydroxylation axis.
In the context of hepatocellular carcinoma, JMJD4-mediated regulation of translation and hypoxia adaptation is particularly significant. Hierarchical signaling from oxygen and 2-oxoglutarate through JMJD4 to eEF1A1 demethylation controls protein synthesis dynamics that can influence tumor cell survival, proliferation, and metastasis under hypoxic conditions commonly found in liver tumors. This knockout model in SK-HEP-1 cells enables the dissection of JMJD4-dependent mechanisms that may contribute to tumor hypoxia adaptation and translational dysregulation, potentially revealing new therapeutic vulnerabilities.
Researchers can employ these polyclonal knockout cells in a variety of functional studies. Representative applications include assessing eEF1A1 Lys36 methylation status by Western blotting, measuring global translation rates via puromycin incorporation or polysome profiling, and evaluating HIF-1?? stabilization under hypoxia. Additionally, the model facilitates screens for JMJD4-dependent drug sensitivities and assays for cell migration and invasion, providing a comprehensive platform for investigating translational control and epigenetic regulation in liver cancer. For further information or to discuss custom cell engineering services, please contact Ascent Research.
